A conserved interaction that is essential for the biogenesis of histone locus bodies

Xiao Cui Yang, Ivan Sabath, Lalitha Kunduru, Andre J. Van Wijnen, William F. Marzluff, Zbigniew Dominski

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Nuclear protein, ataxia-telangiectasia locus (NPAT) and FLICE-associated huge protein (FLASH) are two major components of discrete nuclear structures called histone locus bodies (HLBs). NPAT is a key co-activator of histone gene transcription, whereas FLASH through its N-terminal region functions in 3′ end processing of histone primary transcripts. The C-terminal region of FLASH contains a highly conserved domain that is also present at the end of Yin Yang 1-associated protein-related protein (YARP) and its Drosophila homologue, Mute, previously shown to localize to HLBs in Drosophila cells. Here, we show that the C-terminal domain of human FLASH and YARP interacts with the C-terminal region of NPAT and that this interaction is essential and sufficient to drive FLASH and YARP to HLBs in HeLa cells. Strikingly, only the last 16 amino acids of NPAT are sufficient for the interaction. We also show that the C-terminal domain of Mute interacts with a short region at the end of the Drosophila NPAT orthologue, multi sex combs (Mxc). Altogether, our data indicate that the conserved C-terminal domain shared by FLASH, YARP, and Mute recognizes the C-terminal sequence of NPAT orthologues, thus acting as a signal targeting proteins to HLBs. Finally, we demonstrate that the C-terminal domain of human FLASH can be directly joined with its N-terminal region through alternative splicing. The resulting 190-amino acid MiniFLASH, despite lacking 90% of full-length FLASH, contains all regions necessary for 3′ end processing of histone pre-mRNA in vitro and accumulates in HLBs.

Original languageEnglish (US)
Pages (from-to)33767-33782
Number of pages16
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Dec 5 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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